Analysis of the antibacterial efficacy of modified purines derivatives

Abstract

Recently, it was postulated that antimicrobial substances kill bacteria by a common mechanism involving the formation of reactive oxygen species, in addition to particular drug-target interactions (ROS). However, there is a lot of controversy about this mechanism that produces hydroxyl radicals. Different experimental approaches are anticipated to be the root of the inconsistent results because the role of ROS to antibiotic-mediated death most likely varies on the circumstances. In the current work, the bacteria strains Escherichia coli, Sarcina lutea, Bacillus cereus, and Proteus mirabilis were treated with nucleoside-based compounds 2-F-araA, 2-F-araAMP and NH2-6-Cl-araPur, and the formation of reactive oxygen species (ROS) was measured. The formation of intracellular reactive ROS was shown to be increased over time by the examined modified pyrimidine nucleoside derivatives (validated via DCFA-DA probe assay). For instance, an increase in the ROS was measured in E. coli after treatment with NH2-6-Cl-araPur but not after treatment with 2-FaraA, and2-F-araAMP. Results also vary depending on the species studied and the experimental setup. Despite this, our data strongly imply that using antioxidants as therapeutic agents to treat some infections is a viable option that is starting to be used against bacterial strains.